2007 PhD (Microbial Pathogenesis) Stony Brook University, Stony Brook, NY
1998 MS (Microbiology) MES’ Abasaheb Garware College, University of Pune, Pune, India
1996 BS (Microbiology) MES’ Abasaheb Garware College, University of Pune, Pune, India
Areas of Research: Mucosal Immunology, Inflammasome Biology, Environmental Exposures (secondhand cigarette smoke)
I am an Immunologist/Microbiologist with broad research interests and training in mucosal immunology, cell biology, bacterial genetics and animal models of infection. The goal of the research program in my laboratory is to gain molecular and cellular insights into the complex interactions between bacterial pathogens and their human host. Currently, we are studying two main lines of research in my laboratory:
1. Cigarette Smoke and Respiratory Tract Infections
The main objective of this research project is to delineate the complex molecular interplay between cigarette smoke chemicals, host innate immunity and bacterial virulence. The human nasopharyngeal epithelium, a sentinel site of respiratory immunity, is constantly inhabited by the normal microbiota, which includes highly pathogenic (and deadly) pathogens such as Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae. Our publications support that the oxidant chemicals in cigarette smoke suppress the epithelial detection of microbial products while inducing the virulence of respiratory pathogens such as Staphylococcus aureus. We use a mouse model of nasal colonization as well as high-throughput techniques such as RNA-seq. In addition, primary cell cultures of murine/human phagocytes (neutrophils and macrophages) are used to determine why smoke-exposed bacterial are significantly better at escaping innate immune defenses such as phagocytosis and intracellular killing.
2. Molecular Pathophysiology of Bacterial Urinary Tract Infections
Urinary tract infection (UTI) is a highly prevalent and resource-taxing disease worldwide. Uropathogenic Escherichia coli (UPEC) is the principal causative agent of UTI. The main obstacle in the successful treatment of UPEC-UTI is the continual emergence of drug-resistant strains, propensity for recurrence and unavailability of a licensed vaccine. Over last three decades, substantial research effort has been aimed at deciphering UPEC virulence mechanisms and host immune responses during UTI. The main goal of this project is to define the role of NLRP3 inflammasomes in the immune defense against different uropathogenic bacteria. We use techniques in molecular microbiology and immunology (quantitative real-time PCR, western blot, ELISA, FACS) to monitor the progression of UTI in a mouse model of ascending UTI.
Some of the important techniques used in our lab:
Mouse model of intranasal colonization
Mouse model of intra-tracheal inoculation
Mouse model of ascending UTI
SDS-PAGE and western blot
Quantitative real-time PCR
Bacterial and eukaryotic transcriptome analysis by RNAseq (RNA sequencing)
I encourage post-docs and students (graduate and undergraduate) interested in working in my lab to contact me email@example.com
Selected Peer-reviewed Publications
1. Kulkarni R$, Caskey J, Singh S, Paudel S, Baral P, Schexnayder M*, Kim J, Kim N, Kosmider B, Ratner AJ, Jeyaseelan S. CSE exposed MRSA does not modulate leukocyte recruitment but regulates leukocyte function for persistence in the lungs Am J Respir Cell Mol Biol 2016 Oct; 55(4):586-601 $Corresponding author
2. Amaral FE*, Parker D, Randis TM, Kulkarni R, Prince AS, Shirasu-Hiza MM, Ratner AJ. Rational manipulation of mRNA folding free energy allows rheostat control of pneumolysin production by Streptococcus pneumoniae. PLoSONE 2015 DOI 10.1371
3. Paragas N#, Kulkarni R#, Werth M#, Schmidt-Ott KM#, Forster C, Deng R, Zhang Q, Singer E, Klose AD, Shen TH, Francis KP, Ray S, Vijayakumar S, Seward S, Bovino ME, Xu K, Takabe Y, Mohan S, Wax R, Corbin K, Sanna-Cherchi S, Mori K, Johnson L, Nickolas T, D’Agati V, Lin C-S, Payne S, Qiu A, Al-Awqati Q, Ratner AJ and Barasch J. The α-Intercalated Cell Defends the Urinary System from Bacterial Infection. J Clin Invest. 2014 Jul; 124(7): 2963-76. # equal contribution.
4. Leissinger M, Kulkarni R, Zemans RL, Downey GP, Jeyaseelan S Investigating the role of NOD-like receptors in bacterial lung infections. Review Am J Respir Crit Care Med. 2014 Jun; 189(12):1461-8.
5. Kulkarni R, Jeyaseelan S Strangers with candy: policing the lungs with C-type lectins. Invited editorial. J Leukoc biol 2013;94(3):387-9
6. Kulkarni R, Randis TM, Antala S*, Wang A*, Amaral FA, Ratner AJ βH/C of group B streptococci enhances host inflammation but is dispensable for establishment of urinary tract infection. PLoSONE 2013, 8(3):e59091.
7. Kulkarni R, Antala S, Wang A, Amaral FA, Rampersaud R, Ratner AJ Cigarette smoke increases Staphylococcus aureus biofilm formation via oxidative stress. Infect Immun 2012; 80(11):3804-11.
8. Paragas N, Qiu A, Zhang Q, Samstein B, Deng SX, Schmidt-Ott KM, Viltard M, Yu W, Forster CS, Gong G, Liu Y, Kulkarni R, Mori K, Kalandadze A, Ratner AJ, Devarajan P, Landry DW, D'Agati V, Lin CS, Barasch J. The Ngal reporter mouse detects the response of the kidney to injury in real time. Nature Medicine 2011; 17(2): 216-22.
9. Rampersaud R, Planet PJ, Randis TM, Kulkarni R, Aguilar JL, Lehrer RI, Ratner AJ. Inerolysin, a cholesterol-dependent cytolysin produced by Lactobacillus iners. J Bacteriol 2011; 193(5): 1034-41.
10. Kulkarni R, Rampersaud R, Aguilar JL, Randis TM, Kreindler JL, Ratner AJ. Cigarette smoke inhibits airway epithelial innate immune responses to bacteria. Infect Immun 2010; 78(5): 2146-52.
11. Aguilar JL, Kulkarni R, Randis TM, Soman S, Kikuchi A, Yin Y, Ratner AJ. Phosphatase-dependent regulation of epithelial mitogen-activated protein kinase responses to toxin-induced membrane pores. PLoS ONE 2009; 4(11): e8076.